12-55695573-C-T

Position:

chr12-55695573-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002206.3(ITGA7):c.1952G>A(p.Arg651His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,612,848 control chromosomes in the GnomAD database, including 233,196 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 20346 hom., cov: 28)

Exomes 𝑓: 0.53 ( 212850 hom. )

Consequence

ITGA7
NM_002206.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0920

Variant links:

Genes affected

ITGA7 (HGNC:6143): (integrin subunit alpha 7) The protein encoded by this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. They mediate a wide spectrum of cell-cell and cell-matrix interactions, and thus play a role in cell migration, morphologic development, differentiation, and metastasis. This protein functions as a receptor for the basement membrane protein laminin-1. It is mainly expressed in skeletal and cardiac muscles and may be involved in differentiation and migration processes during myogenesis. Defects in this gene are associated with congenital myopathy. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Feb 2009]

ITGA7 links:

ITGA7 (HGNC:):

ITGA7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.2049737E-7).

BP6

Variant 12-55695573-C-T is Benign according to our data. Variant chr12-55695573-C-T is described in ClinVar as [Benign]. Clinvar id is 94035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55695573-C-T is described in Lovd as [Benign]. Variant chr12-55695573-C-T is described in Lovd as [Likely_pathogenic].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA7	NM_002206.3 linkuse as main transcript	c.1952G>A	p.Arg651His	missense_variant	14/25	ENST00000257879.11	NP_002197.2	Q13683-7Q4LE35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA7	ENST00000257879.11 linkuse as main transcript	c.1952G>A	p.Arg651His	missense_variant	14/25	1	NM_002206.3	ENSP00000257879.7		Q13683-7

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75757

AN:

151416

Hom.:

20333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.574

Gnomad AMR

AF:

0.600

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.935

Gnomad SAS

AF:

0.716

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.510

Gnomad OTH

AF:

0.481

GnomAD3 exomes

AF:

0.592

AC:

148860

AN:

251382

Hom.:

46925

AF XY:

0.593

AC XY:

80621

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.328

Gnomad AMR exome

AF:

0.714

Gnomad ASJ exome

AF:

0.456

Gnomad EAS exome

AF:

0.939

Gnomad SAS exome

AF:

0.697

Gnomad FIN exome

AF:

0.650

Gnomad NFE exome

AF:

0.512

Gnomad OTH exome

AF:

0.549

GnomAD4 exome

AF:

0.530

AC:

773992

AN:

1461314

Hom.:

212850

Cov.:

AF XY:

0.534

AC XY:

388526

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.318

Gnomad4 AMR exome

AF:

0.700

Gnomad4 ASJ exome

AF:

0.460

Gnomad4 EAS exome

AF:

0.935

Gnomad4 SAS exome

AF:

0.692

Gnomad4 FIN exome

AF:

0.641

Gnomad4 NFE exome

AF:

0.498

Gnomad4 OTH exome

AF:

0.530

GnomAD4 genome

AF:

0.500

AC:

75800

AN:

151534

Hom.:

20346

Cov.:

AF XY:

0.514

AC XY:

38044

AN XY:

74034

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.600

Gnomad4 ASJ

AF:

0.454

Gnomad4 EAS

AF:

0.935

Gnomad4 SAS

AF:

0.714

Gnomad4 FIN

AF:

0.652

Gnomad4 NFE

AF:

0.510

Gnomad4 OTH

AF:

0.485

Alfa

AF:

0.511

Hom.:

50192

Bravo

AF:

0.485

TwinsUK

AF:

0.497

AC:

1842

ALSPAC

AF:

0.498

AC:

1921

ESP6500AA

AF:

0.340

AC:

1497

ESP6500EA

AF:

0.508

AC:

4373

ExAC

AF:

0.585

AC:

71060

Asia WGS

AF:

0.768

AC:

2667

AN:

3478

EpiCase

AF:

0.497

EpiControl

AF:

0.494

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 18, 2012	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 20, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 04, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Congenital muscular dystrophy due to integrin alpha-7 deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0019

.;.;T;.;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.0035

LIST_S2

Benign

0.79

T;T;T;T;T

MetaRNN

Benign

9.2e-7

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;.;.;.;N

PrimateAI

Benign

0.21

PROVEAN

Benign

1.4

N;N;N;N;N

REVEL

Benign

0.088

Sift

Benign

0.28

T;T;T;T;T

Sift4G

Benign

0.45

T;T;T;T;T

Polyphen

0.0

B;.;.;B;B

Vest4

0.066

MPC

0.21

ClinPred

0.0057

GERP RS

-0.71

Varity_R

0.013

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over